This study will test the safety and side effects of an experimental vaccine booster against HIV. A vaccine is a substance given to try to create immunity or resistance to a disease or infection. The vaccine used in this study is called VRC-HIVADV014-00-VP. It is made from an adenovirus (a common virus that causes upper respiratory infections) that contains DNA (genetic material) of three HIV proteins. Injected into a human, the viral DNA instructs the body to make small amounts of some HIV proteins. VRC-HIVADV014-00-VP will be given to people who previously received a vaccine called VRC-HIVDNA009-00-VP under NIH protocol 03-I-0022. Important: Study participants cannot catch an adenovirus infection or HIV or AIDS from the vaccine or any proteins made from it.

Healthy normal volunteers who participated in NIH protocol 03-I-0022 may be eligible for this study. They must have completed three injections of 4 mg or 8 mg of VRC-HIVDNA009-00-VP without experiencing a serious side effect that was possibly related to the vaccine. Candidates are screened with a medical history, clinical evaluation, blood and urine tests, and HIV and pregnancy counseling.

Participants receive one injection of VRC-HIVADV014-00-VP the day they enroll in the study (study day 0). They are observed for at least 30 minutes after immunization. At home, they record their temperature and any symptoms they may experience, including any effects at the injection site, for 5 days and call a study nurse 1 or 2 days after the injection. They immediately report any symptoms to the clinic staff and, if necessary, come to the clinic for an examination.

Participants have five additional clinic visits during the study, at weeks 2, 4, 6, 12 and 24, each lasting about 2 hours. At each visit, they are checked for health changes or problems and are asked about medications they are taking. Blood is drawn for immune function testing, HLA typing (a genetic test of immune system markers), and other genetic factors. A urine sample is collected at some visits. Additional laboratory tests may be requested between visits. Some participants may undergo apheresis at the week 4 visit to collect a large number of white blood cells for laboratory tests to see how the immune system responds to the study vaccine. For this procedure, blood is collected through a needle in an arm vein and flows through a catheter (plastic tube) into a machine that separates it into its components by centrifugation (spinning). The white cells are extracted and the rest of the blood is returned through another needle in the other arm. The procedure takes about 1 to 3 hours.

Participants are tested three or more times for HIV and are questioned about their sexual behavior and drug use. They complete a "social impact" questionnaire at week 24 that includes questions about any problems they may have experienced from their participation in the study regarding such things as insurance, health care, friends, family, employment, housing, education, or government agencies.

A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of a Booster Dose of a Recombinant Multiclade HIV-1 Adenoviral Vector Vaccine, VRC-HIVADV014-00-VP, in Uninfected Subjects Who Were Previously Immunized With VRC-HIVDNA009-00-VP in VRC 004

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment:

32

Study Start Date:

January 2005

Estimated Study Completion Date:

October 2007

Detailed Description:

Study Design: This is a Phase I open-label study to examine safety, tolerability and immune response of a multiclade HIV adenoviral vector vaccine as a booster vaccination in uninfected adults. The hypothesis is that this vaccine will be safe as a booster vaccine and elicit immune responses to HIV. The primary objective is to evaluate the safety and tolerability of a VRC-HIVADV014-00-VP booster vaccination in uninfected subjects who previously received 3 injections of VRC-HIVDNA009-00-VP more than one year prior to the study vaccination. The secondary objectives include immunogenicity evaluations and adenovirus serotype 5 (Ad5) antibody titers, and social impacts. Exploratory evaluations include epitope mapping and other immunogenicity evaluations.

Subjects: Healthy adult volunteers who previously received three injections of VRC-HIVDNA009-00-VP at a dosage of 4 mg or 8 mg in the VRC 004 study (03-I-0022): subjects in these groups were between 20 and 39 years old at time of enrollment in VRC 004; those who participate in VRC 009 will be approximately 1-3 years older at the time of enrollment into VRC 009.

Study Plan: Up to thirty-two volunteers will receive one 1 mL injection of the study agent at a dosage of 1 x 10(10) PU IM in a deltoid muscle. Safety and immunogenicity will be evaluated by follow-up visits over the subsequent 24 weeks. The peripheral blood mononuclear cell (PBMC) sample for immunogenicity studies collected at Week 4 after vaccination will be obtained by apheresis if the subject is willing and eligible for apheresis and an apheresis appointment can be conveniently scheduled in the interval specified; otherwise PBMCs will be obtained from 80 mL blood collected by phlebotomy.

Study Duration: Subjects will be evaluated at 6 or more clinical visits for 24 weeks after the study injection.

Study Endpoints: The primary endpoint is safety of the vaccine administered at a dose of 1 x 10(10) particle units (PU) by intramuscular injection. Secondary endpoints are immunogenicity as indicated by HIV-specific antibody and cellular immune responses through Week 6, Ad5 antibody titer at Week 0 and Week 4 and social impact at Week 24. Exploratory analyses of immunogenicity at Weeks 12 and 24, Ad5 antibody titer at Week 24 and epitope mapping of the CD8+ and CD4+ T cell responses at Week 4.

Eligibility

Ages Eligible for Study:

18 Years to 50 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

INCLUSION CRITERIA:

A participant must meet all of the following criteria:

Completed three injections of 4 mg or 8 mg of study vaccine in VRC 004 (03-I-0022) without experiencing a serious adverse event (SAE) that was possibly, probably or definitely related to study vaccine.

Available for clinical follow-up for 24 weeks after enrollment.

Completion of an Assessment of Understanding prior to enrollment and able to verbalize understanding of all questions answered incorrectly.

Able and willing to complete the informed consent process.

Willing to receive HIV test results and willing to abide by NIH guidelines for partner notification of positive HIV results.

Willing to donate blood for sample storage to be used for future research.

male partner has previously undergone a vasectomy for which there is documentation.

EXCLUSION CRITERIA:

A volunteer will be excluded if one or more of the following conditions apply:

Women:

Breast-feeding or planning to become pregnant during the 24 weeks of study participation.

Volunteer has received any of the following substances:

Immunosuppressive or cytotoxic medications or inhaled corticosteroids within the past six months (with the exception of corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for an acute uncomplicated dermatitis).

Blood products within 120 days prior to HIV screening.

Immunoglobulin within 60 days prior to HIV screening.

Live attenuated vaccines within 30 days prior to initial study vaccine administration.

Investigational research agents within 30 days prior to study vaccine administration.

Syphilis infection that is active or a positive serology due to a syphilis infection treated less than six months ago.

Malignancy that is active or treated malignancy for which there is not reasonable assurance of sustained cure or malignancy that is likely to recur during the period of the study.

Seizure disorder other than: 1) febrile seizures under the age of two, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) a singular seizure not requiring treatment within the last 3 years.

Asplenia or any condition resulting in the absence or removal of the spleen.

Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder requiring therapy that has not been well controlled on medication for the past two years; disorder requiring lithium; or suicidal ideation occurring within five years prior to enrollment.

Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00102089